What is erythropoietic protoporphyria (EPP)?
Erythropoietic protoporphyria (EPP) is a rare metabolic disorder that causes severe anaphylactoid reactions to light (phototoxicity).
EPP belongs to a family of disorders called porphyrias that are all associated with unusually high levels of compounds called porphyrins or precursors of porphyrins which cause tissue damage. Porphyrins are products used in the making of haem (sometimes spelled heme) which is essential to many functions in the body.
In healthy humans the production of haem follows a specific pathway, with enzymes (proteins which perform a specific task) binding and converting a series of chemical products to produce haem. In the final step of this pathway an iron molecule is bound to protoporphyrin IX (PPIX) by the enzyme ferrochelatase (FECH) to form haem. EPP patients have a marked deficiency of this enzyme, due to a genetic mutation in the FECH gene, which encodes the ferrochelatase protein. The insufficient activity of ferrochelatase means that PPIX cannot be converted to haem, resulting in the accumulation of PPIX in bone-marrow cells, the skin and the liver. The storage of PPIX leads to tissue damage and destruction of blood vessels.
Almost all EPP patients inherit two mutations (genetic defects) from their parents. A combination of two mutations is required to cause EPP, however, and thus siblings of an EPP patients have a 1 in 4 chance of inheriting the disease.
Read more about the cause and inheritance of EPP.
Signs and Symptoms
Symptoms of erythropoietic protoporphyria typically begin in childhood. Patients incur physical burns and ulcers, and are in a state of crisis following light exposure, summarised as phototoxicity. This usually occurs within minutes of exposure to bright lights, especially sunlight. EPP symptoms can be acute, or delayed (subacute), most often expressed as generalised oedema, effusion in tissue and distortion of the skin.
As little as a few minutes of light outdoors (even when it is overcast or transmitted through a window) or artificial light exposure may be sufficient to evoke EPP symptoms. Phototoxicity is unresponsive to traditional pain and burn management techniques and patients can be incapacitated for days before reactions subside. Most patients withdraw from light exposure in order to manage their phototoxic symptoms.
Read more about phototoxicity in EPP.
Erythropoietic protoporphyria patients will sometimes have a mild anaemia, presumably due to the reduced ability to form haem. This anaemia can be confused with iron-deficiency anaemia. Gall stones, usually pigment stones, are more common at an earlier age in EPP patients than in the general population.
Liver problems including jaundice, cirrhosis and even liver failure occur in a small number of erythropoietic protoporphyria patients – understood to be less than 3-5%. The liver problems are thought to be due to very high levels of protoporphyrin IX accumulating in the liver and small bile passages. The liver is the only organ which is capable of ridding the body of protoporphyrin IX, which it does by excreting the porphyrin into the bile. Liver failure is an extremely dangerous and potentially fatal complication, which requires urgent treatment and, in many cases, liver transplantation.
Because many patients do not have permanent, visible skin changes, the diagnosis of EPP is often missed or delayed by many years.
Read more about complications in EPP.
The diagnosis of erythropoietic protoporphyria is based on finding increased levels of free protoporphyrin IX in red blood cells. The protoporphyrin measurements should ideally be performed by a certified laboratory with expertise in porphyria diagnostics. Genetic testing can confirm the mutations in the FECH gene. Most testing is performed only after patients report symptoms to a medical professional who has been able to recognise and diagnose the condition, although initial self-diagnosis, particularly with the aid of online search engines, has occasionally been reported.
Read more about the diagnosis of EPP.
Erythropoietic protoporphyria symptoms and episodes are usually relatively consistent throughout life.